This work involves studies on the structure, function and maintenance of bacterial plasmids in the genus Streptococcus. Emphasis is being placed on a multiple drug resistant strain of Streptococcus faecalis harboring three plasmids, each of which determines either drug resistance (erythromycin, lincomycin, or tetracycline) or toxin (hemolysin) production. One of the plasmids (the toxin-determining plasmid) is transmissible, capable of being transferred to other S. faecalis strains, presumably by conjugation. This plasmid also is capable of mobilizing one of the otherwise non-transmissible plasmids in this strain. Another plasmid, which determines tetracycline resistance, is capable of undergoing a reversible amplification phenomenon with respect to a certain region on the molecule (presumably the tetracycline-resistance determinant) when the cells are grown for a prolonged period of time (e.g., 25-50 generations) in the presence of drug. Efforts are being made to determine the molecular processes involved in this phenomenon. BIBLIOGRAPHIC REFERENCES: Clewell, D., Yagi, Y. 1976. Amplification of the tetracycline resistance determinant on plasmid pAMalpha1 in Streptococcus faecalis. In DNA Insertion Elements, Plasmids and Episomes. (Bukhari and Shapiro, Ed.), Cold Spring Harbor Press, in press. Clewell, D. and Yagi, Y. l976. Recombination sequences and the amplification of the tetracycline-resistance determinant in plasmid pAMalpha1 of Streptococcus faecalis. In proceedings of the "Third Symposium on Plasmids and Antibiotic Resistance", (Krcmery and Rosival, Ed.), Springer Verlag, N.Y., in press.